"A variable epitope library approach to the development of more broadly protective porcine reproductive and respiratory syndrome vaccines"

Porcine reproductive and respiratory syndrome viruses (PRRSV) are responsible for one of the most economically important diseases affecting the global pig industry, estimated at over US$ 600 million and € 1.5 billion p.a. in the USA and Europe, respectively. PRRSV mutates continuously, including changes to epitopes on the glycoproteins that comprise the minor envelope complex (GP2, GP3 and GP4) that enables escape from vaccine-induced antibodies. This has led to the generation of a high level of antigenic diversity which makes controlling PRRSV by conventional vaccines challenging.

This project aims to evaluate a novel vaccine technology that may offer a pathway to more broadly protective PRRS vaccines. The technology involves delivery of a library of viral antigens (via DNA/RNA vectors) which are all based on consensus sequence of PRRSV glycoproteins but with the exception that the coding sequence of each variable epitope is replaced with the coding sequence of the same area derived from previously reported strains. We hypothesise that immunisation with the variable epitope library will result in the immune system ignoring these epitopes due to their high variability in the vaccine conformation, and instead direct itself towards more conserved, normally subdominant, epitopes. Alternatively, the immune system may respond to multiple versions of the hypervariable epitope region, thereby eliciting a more broadly reactive polyclonal response.

The project will address this aim through the following objectives:

1.     Define and curate hypervariable epitopes of PRRSV-1 GP2, GP3 and GP4 based on previously identified and publicly available sequences.

2.     Construct variable epitope libraries by introducing degenerate sequences into hypervariable epitope regions of GP2, GP3 and GP4.

3.     Evaluate the immunogenicity of DNA vector encoded variable epitope libraries in mice.

4.     Evaluate the immunogenicity of self-amplifying (sa)RNA vector encoded variable epitope libraries in pigs (dependent upon securing additional funding).

The student will be guided by an experienced team of supervisors who bring complimentary expertise to support all aspects of this project (Gould/Sadigh – molecular virology and Graham/De Brito – PRRS immunology and vaccinology). Supervision will be on a day-to-day basis initially, especially during the first year and during specific training. Confidence and independence will be nurtured, with an anticipated reduction in supervisory requirement as the project matures and the student becomes more independent in experimental design, application, and analysis. Progress will be monitored informally by the student reporting in bi-weekly lab meetings at Pirbright and formally via monthly videoconferences with all supervisors at CU and Pirbright. This project offers a fantastic opportunity for the student to master numerous state-of-the-art molecular biology, virology, and immunology techniques. The student will spend the first stage of the project at CU constructing the variable epitope libraries. They will then bring the libraries to Pirbright for further characterisation, including the evaluation of their immunogenicity in mice and potentially pigs. In addition to developing technical skills, the supervisory team will support the student’s development of a range of ‘soft skills’ including critical thinking, communication, and teamworking.

The student will be based primarily at The Pirbright Institute and registered with the University of Coventry. The student will visit the university to meet with their supervisors and undertake training or complete specific project tasks as required.

This studentship is open to science graduates with, or who anticipate obtaining, at least a 2:1 or equivalent, in a relevant biological subject in their undergraduate degree, or a Masters degree - subject to university regulations. Other first degrees, e.g. veterinary science, will be considered. You should be looking for a challenging, interdisciplinary research training environment and have an active interest in the control of infectious diseases.

Students without English as a first language must provide evidence that they meet the English language requirement, e.g. with an average IELTS score of 7.0, with no lower than 7.0 in listening/reading and no lower than 6.5 in speaking/writing.

TO APPLY: Full details of how to apply can be found on our website: How to apply | The Pirbright Institute

For informal enquiries regarding this project please contact the project supervisors. For enquiries regarding eligibility and the application process please email [Email Address Removed]